Role of bone morphogenic protein 2 in retinal patterning and retinotectal projection
Role of bone morphogenic protein 2 in retinal patterning and retinotectal projection
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DOI：
10.1523/jneurosci.3027-06.2006
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发表时间：
2006-10-18
影响因子：
5.3
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
--
作者：
Sakuta, Hiraki;Takahashi, Hiroo;Noda, Masaharu
长期以来，人们一直认为发育中的视网膜的前前轴（A-P）和后腹轴（D-V）是独立决定的，并且沿这两个轴的视网膜顶投影是独立控制的。然而，我们最近证明，在发育中的鸡视网膜中，骨形态发生蛋白（BMP）拮抗剂Ventroptin的错误表达不仅会改变沿D-V（或中外侧）轴的视网膜顶投影，还会改变沿a - p轴的视网膜顶投影。此外，BMP4的背侧高表达在胚胎第5天（E5）被BMP2的背侧颞侧高表达所缓解，在此期间，Ventroptin分别持续抵消两种bmp保持反梯度表达模式。在这里，我们发现到目前为止报道的仅沿D-V轴具有梯度的地形分子和仅沿a - p轴具有梯度的ephrin-A2都受BMP信号的控制，并且它们在发育中的鸡视网膜中从E6开始沿着倾斜轴以梯度方式表达：当BMP2在发育中的表达被操纵时，这些倾斜梯度分子的表达模式都发生了变化。此外，在BMP2敲低的胚胎和ephrin- a2错误表达的胚胎中，视网膜顶沿两个正交轴的投影都发生了改变。因此，BMP4到BMP2的表达转换似乎在视网膜发育过程中通过将D-V轴向后侧倾斜，在视网膜模式和视网膜顶的地形投影中起关键作用。我们的研究结果还表明，BMP2的表达对于维持修改后的D-V轴的区域特异性至关重要。
It has been long believed that the anteroposterior (A-P) and dorsoventral (D-V) axes in the developing retina are determined independently and also that the retinotectal projection along the two axes is controlled independently. However, we recently demonstrated that misexpression of Ventroptin, a bone morphogenic protein (BMP) antagonist, in the developing chick retina alters the retinotectal projection not only along the D-V (or mediolateral) axis but also along the A-P axis. Moreover, the dorsal-high expression of BMP4 is relieved by the dorsotemporal-high expression of BMP2 at embryonic day 5 (E5) in the retina, during which Ventroptin continuously counteracts the two BMPs keeping on the countergradient expression pattern, respectively. Here, we show that the topographic molecules so far reported to have a gradient only along the D-V axis and ephrin-A2 so far only along the A-P axis are both controlled by the BMP signal, and that they are expressed in a gradient manner along the tilted axis from E6 on in the developing chick retina: the expression patterns of these oblique-gradient molecules are all changed, when BMP2 expression is manipulated in the developing retina. Furthermore, in both BMP2 knockdown embryos and ephrin-A2-misexpressed embryos, the retinotectal projection is altered along the two orthogonal axes. The expressional switching from BMP4 to BMP2 thus appears to play a key role in the retinal patterning and topographic retinotectal projection by tilting the D-V axis toward the posterior side during retinal development. Our results also indicate that BMP2 expression is essential for the maintenance of regional specificity along the revised D-V axis.